Squashing superbugs

Some bacteria are resistant to disinfectants—but not for much longer.

By Katharine Coggeshall | December 1, 2020

Bacteria Sanitizer Graphic Opt
With each spritz of hand sanitizer comes an opportunity for the emergence of a superbug—a bacterium that is resistant to antibacterial agents. Los Alamos National Laboratory

Since the outbreak of the novel coronavirus pandemic, hand sanitizer, antibacterial soap, and bacteria-killing cleaning products have flown off supermarket shelves. But with each spritz and squeeze comes an opportunity for the emergence of a superbug—a bacterium that is resistant to antibacterial agents.

“We’ve developed and patented a topical antiseptic called choline generate, nicknamed CAGE.”
- David Fox

How is it possible that using products meant to kill bacteria can end up making some bacteria stronger? It comes down to percentages and evolution. When antibacterial soaps and cleansers are used to kill bacteria, they never kill 100 percent of the population. Some germs don’t die because they possess a helpful genetic mutation (such as a gene that enables antibiotic resistance) or they’ve achieved what’s called a persister state, which allows them to ride out the environmental inconvenience of an antibiotic without getting killed.

This persister state isn’t well understood, but it is documented. “Persister cells are genetically identical to the susceptible bacterial cells in a population,” says Sofiya Micheva-Viteva, a bioscientist at Los Alamos National Laboratory, “but they are able to persist when an environmental stressor (such as an antibiotic) is present.”

Outwardly, persister cells seem dormant—almost as if they can sleep through the antibiotic attack—but inside, they are busy reorganizing their metabolism and fortifying their defenses. “Persister cells can spontaneously activate specific gene clusters that help them survive environmental stress,” Micheva-Viteva continues. Even though the rest of the bacterial cells possess the same genes, they don’t turn them on the way the persister cells do.

So, how much of a given bacterial population is considered persistent? This trait is actually quite rare, with fewer than one percent able to resist antibiotics. But that little amount is enough to create a big problem, especially during a pandemic. Not only are people overcleaning with unnecessary antibacterials—good old soap and water will get the job done—but more antibiotics are being prescribed as a result of the pandemic (often, when people get sick from coronavirus, bacteria cause a secondary infection, such as bacterial pneumonia, which is treated with antibiotics). This rampant antibacterial use is speeding up the evolution of superbugs by providing more opportunities for antibiotic-resistant bacteria to thrive.

But prescribing antibiotics for an infection isn’t the only way the door is opened for superbugs. Wiping down a grocery cart handle with an antibacterial wipe rids the surface of susceptible bacteria, but it leaves behind the unstoppable persister cells. The superbugs can now reproduce at will, creating larger populations of antibiotic-resistant germs.

This scenario gets worse as these superbugs find new homes on skin and particularly in wounds, where superbugs are protected by a slimy matrix of bacterial cells, sugars, and proteins. “Antibiotic-resistant bacteria in wounds can be really detrimental,” says David Fox of the Laboratory’s Actinide Analytical Chemistry group. “It can lead to amputation of a limb or even mortality.”

Fox has studied several superbugs that fall into a pathogen category known as ESKAPE. ESKAPE is a known grouping of six multidrug-resistant bacteria: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and the Enterobacter species. These pathogens are extremely resistant to traditional therapeutic agents. In other words, they are superbugs, noted by the World Health Organization as high priority in terms of urgently requiring the development of new antibiotic treatments. Fox has been working on just that.

“We’ve developed and patented a topical antiseptic called choline generate, nicknamed CAGE, that is essentially an ionic (chemically charged) liquid that is applied to the skin, similar to a lotion,” Fox explains. “It can penetrate the biofilms these superbugs make and thin their cell membranes.”

In other words, Fox has discovered a treatment that can kill the unkillable ESKAPE pathogens, and it’s a fair bet that CAGE could also be effective against new superbugs. However, CAGE still needs approval from the U.S. Food and Drug Administration (FDA) before it’s ready for widespread human use. Once CAGE is FDA approved, Fox envisions it as being available with a simple doctor’s prescription, and eventually CAGE could be an over-the-counter treatment similar to Neosporin (but far more effective against resistant bacteria).

In studies with mice, CAGE was nontoxic and not irritating, which Fox says is because the antiseptic is made from FDA-approved GRAS (generally recognized as safe) ingredients. Since the mouse studies, CAGE has been patented and is ready for human testing. Fox is now collaborating with Northern Arizona University to build CAGE into a form that can be used on a bandage. Which means that hopefully, in the not-too distant future, squashing superbugs will be as easy as slapping on a Band-Aid.

David Fox Lab
David Fox demonstrates how his patented antiseptic kills methicillin-resistant Staphylococcus aureus (aka the MRSA superbug) in less than 30 seconds.